UNCERTAINTY ABOUT EFFECTS IS A KEY FACTOR INFLUENCING INSTITUTIONAL REVIEW BOARDS' APPROVAL OF CLINICAL STUDIES

Purpose: To investigate factors which influence Institutional Review Board (IRB) members’ decision to approve or not approve clinical studies.

Method: We conducted a vignette based survey over the internet. The vignettes depicted clinical study designs (phase I, II, III trial and observational study) in which uncertainties and six other factors potentially influencing approval of research studies were used. We used a factorial design whereby seven aspects were randomly varied in each vignette to produce unique vignettes for each respondent.  Each participant reviewed 9 vignettes (4 for each study design and 1 randomly selected vignette). At the end of each vignette participants responded to the question regarding their likelihood to approve the proposed study on a 7-point Likert-type scale. Participants also responded to the open-ended question, “Please briefly describe what factors influenced your decision to approve or not approve the proposed study.” Two team members independently conducted thematic content analysis of qualitative responses to the open ended question and categorized the responses into the nine a priori themes or an emergent theme. Partially mixed concurrent dominant status design was employed.  Quantitative component was assigned more weight and mixing occurred at the data interpretation.  We investigated the association between themes and approval decision by adjusting for multiple observations per person by applying the random-effect logit model.

Result: Our study included 230 IRB members from 42 institutions.  Majority of the respondents had experience conducting clinical research (74%) and training in research ethics (65%). Ninety percent (N=208) of these participants provided responses to the open ended question which were classified into 16 themes (9 a priori and 7 emerging themes). Uncertainty, adherence, study design, and harms were frequently and intensely cited to influence study approval. Analysis of two extreme subgroups (approvers vs. non-approvers) showed that uncertainty influenced approval decisions, odds ratios (OR) =3.5 (95%CI: 1.3-9.8) and OR=3.2 (95%CI: 1.1-8.9), respectively, based on theme frequency and theme intensity, ignoring multiple observations per person. Taking into consideration multiple observations per person, similar results were obtained for uncertainty: OR= 8.9(95%CI: 0.93-85.4).

Conclusion: Uncertainty regarding therapeutic efficacy is critical in IRB members' approval of clinical trials. This indicates that before approving the trials, IRBs should introduce the policy to better assess the existing uncertainties in a given trial.